AF is the most common of all cardiac arrhythmias and accounts for nearly one-third of all hospital admissions due to heart rhythm irregularities. In the United States, nearly 2.3 million people suffer from AF2. The prevalence of AF increases with age, afflicting 4% of the population over 60 years old and nearly 9% of persons 80 years and older. With the aging population in this country, AF will be an even larger public health problem in the future. A recent study predicted that the number of Americans diagnosed with AF will grow to over 10 million by the year 2050. Our previous work has led to the development of an anatomic approach for the treatment of AF called the Cox-Maze (CM) procedure. Despite the high degree of efficacy of the operation, with cure rates greater than 90%, it is clear that the procedure is inadequate for some patients, particularly those with large left atria. Furthermore, approximately 20% of patients remain on antiarrhythmic drugs, reducing the drug free cure rate to ~70%. On the other hand, our studies and those of other laboratories have shown that a more limited lesion set can cure AF in certain patient subsets, indicating that some of lesions used in the CM procedure are unnecessary for some patients. The shortcomings of our current surgical procedure call for a new strategy for this arrhythmia and testify to the inadequacy of a single anatomically- based approach for all patients with AF. The overall objective of this grant during the proposed funding period is to improve the efficacy of AF surgery and to minimize its detrimental physiological consequences. The cure rate of AF surgery will be improved by embarking on a novel new operative strategy, by developing a patient- specific lesion set based on an individual patient's anatomy and electrophysiology. These goals will be achieved by the following specific aims: 1: To non-invasively assess mechanisms of AF preoperatively using Electrocardiographic Imaging (ECGI); 2: To develop and test novel patient specific lesion sets based on the critical mass hypothesis and the specific electrophysiological characteristics of the patient's arrhythmia; 3: To develop accurate techniques to evaluate the consequences of AF and surgical ablation on left and right atrial function, both experimentally and clinically. This will allow precise assessment of the hemodynamic consequences of surgery for AF and allow for the development of less damaging procedures. PUBLIC HEALTH RELEVANCE Atrial fibrillation affects over two million Americans and drug therapy is ineffective. Previously, this grant has resulted in the development of a curative procedure called the Cox-Maze procedure. The present proposal is design to improve and simplify this surgical treatment, maintain the high cure rate, and minimize the effects on heart function, thus making it available to a wider patient population.